898 resultados para RATIONALE
Resumo:
The Routledge Guide to Interviewing sets out a well-tested and practical approach and methodology: what works, difficulties and dangers to avoid and key questions which must be answered before you set out. Background methodological issues and arguments are considered and drawn upon but the focus is on what is ethical, legally acceptable and productive:
-Rationale (why, what for, where, how)
-Ethics and Legalities (informed consent, data protection, risks, embargoes)
-Resources (organisational, technical, intellectual)
-Preparation (selecting and approaching interviewees, background and biographical research, establishing credentials, identifying topics)
-Technique (developing expertise and confidence)
-Audio-visual interviews
-Analysis (modes, methods, difficulties)
-Storage (archiving and long-term preservation)
-Sharing Resources (dissemination and development)
From death row to the mansion of a head of state, small kitchens and front parlours, to legislatures and presbyteries, Anna Bryson and Seán McConville’s wide interviewing experience has been condensed into this book. The material set out here has been acquired by trial, error and reflection over a period of more than four decades. The interviewees have ranged from the delightfully straightforward to the painfully difficult to the near impossible – with a sprinkling of those that were impossible.
Successful interviewing draws on the survival skills of everyday life. This guide will help you to adapt, develop and apply these innate skills. Including a range of useful information such as sample waivers, internet resources, useful hints and checklists, it provides sound and plain-speaking support for the oral historian, social scientist and investigator.
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The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.
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Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-b. Exogenous IFN-b restores antiviral activity.
Objectives: To compare the efficacy and safety of inhaled IFN-b with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses.
Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-b (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses.
Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse
(mean change in six-item Asthma Control Questionnaire ,0.5) and IFN-b treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset ofmore difficult-to-treat, Step 4-5 peoplewith asthma (n = 27 IFN-b; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-b (P = 0.004).
Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-b is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the needforfurther, adequately powered, trialsin this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).
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Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.
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Implementation of both design for durability and performance-based standards and specifications are limited by the lack of rapid, simple, science-based test methods for characterizing the transport properties and deterioration resistance of concrete. To this end, this paper presents the background rationale and current developments in the application of electrical property measurements - conductivity in this instance - as a testing methodology to evaluate the relative performance of a range of concrete mixes. The technique can not only be used on standard specimens (e.g. cubes), but also lends itself to in-situ monitoring thereby allowing measurements to be obtained on the as-placed concrete. It is the latter which forms the focus of the current work. Conductivity measurements are presented for concretes with and without supplementary cementitious materials (SCM's) from demoulding up to 400-days. It is shown that electrical conductivity measurements display a continual decrease over the entire test period and attributed to the pore structure refinement due to hydration and pozzolanic reaction in those concretes containing blast furnace slag or fly ash. The term Formation Factor is introduced to rank concrete performance in terms of is resistance to chloride penetration.
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Rationale:
Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family.
Objectives:
In this study, we investigated the hypothesis that airway epithelial cells are a source of CTSS, and mechanisms underlying CTSS expression in the CF lung.
Methods:
Protease activity was determined using fluorogenic activity assays. Protein and mRNA expression were analyzed by ELISA, Western blotting, and reverse-transcriptase polymerase chain reaction.Measurements and Main Results: In contrast to neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples from patients without Pseudomonas aeruginosa infection. In this study, we identified epithelial cells as a source of pulmonary CTSS activity with the demonstration that CF airway epithelial cells express and secrete significantly more CTSS than non-CF control cells in the absence of proinflammatory stimulation. Furthermore, levels of the transcription factor IRF-1 correlated with increased levels of its target gene CTSS. We discovered that miR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion.
Conclusions:
The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.
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The catalyst for this special issue was a symposium entitled Religion, Violence and Cities, held under the auspices of a five year inter-disciplinary research project on ethno-nationally divided cities.
While this project expressly addressed cities divided by ethno-national conflict, it was clear from the beginning that there was an important religious dimension to such conflicts in most, if not all, the cities being studied.2 The rationale of the Special Issue is to examine how this religious dimension exacerbates (or moderates) urban violence within a broad comparative context. Although three of the following articles are informed by Project research, we draw the net wider to encompass a broader geographical spread from the Balkans, the Middle East, Nigeria and Japan.
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The use of surveys and direct feedback from women as a measurement of their maternity experience is seen as a means of stimulating quality improvement. Underpinning the overall rationale behind national maternity surveys is the acknowledgement that there is a need to document women's views of maternity services to inform policymakers with a view to enhancing the delivery of quality care to women. The evidence suggests that using maternity surveys to improve maternity care experience is central to UK health policy. It is also evident that qualitative input from women has the power to highlight mismatches of experience between women and professionals. Trusts are required to look to the future and invest in qualitative methodologies, which elicit rich and detailed information on women's experiences. The aim of this literature review is to critically analyse the use of maternity surveys and their validity in improving the care experienced by users of maternity services.
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Leniency (amnesty) plus is one of the tools used in the fight against anticompetitive agreements. It allows a cartelist who did not manage to secure complete immunity under general leniency, to secure an additional reduction of sanctions in exchange for cooperation with the authorities with respect to operation of another prohibited agreement on an unrelated market. The instrument was developed in the United States and, in recent years, it was introduced in a number of jurisdictions. This article contextualises the operation of and rationale behind leniency plus, forewarning about its potential procollusive effects and the possibility of its strategic (mis)use by cartelists. It discusses theoretical, moral, and systemic (deterrence-related) problems surrounding this tool. It also provides a comparison of leniency plus in eleven jurisdictions, identifying common design flaws. This piece argues that leniency plus tends to be a problematic and poorly transplanted US legal innovation. Policy-makers considering its introduction should analyse it in light of institutional limits and local realities. Some of the regimes which already introduced it would be better off abandoning it.
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In 2009, the Royal Victoria Hospital, Belfast, established a nine-bed, short-stay unit in its emergency department. This article explains the rationale for the model of care delivery adopted, and the importance of developing and working with integrated care pathways. It also discusses four areas essential to the effective running of the unit: interdisciplinary collaboration, training for clinical nurse leaders, management of change and leadership.
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Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation.
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Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments.
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The principle feature in the evolution of the internet has been its ever growing reach to include old and young, rich and poor. The internet’s ever encroaching presence has transported it from our desktop to our pocket and into our glasses. This is illustrated in the Internet Society Questionnaire on Multistakeholder Governance, which found the main factors affecting change in the Internet governance landscape were more users online from more countries and the influence of the internet over daily life. The omnipresence of the internet is self- perpetuating; its usefulness grows with every new user and every new piece of data uploaded. The advent of social media and the creation of a virtual presence for each of us, even when we are not physically present or ‘logged on’, means we are fast approaching the point where we are all connected, to everyone else, all the time. We have moved far beyond the point where governments can claim to represent our views which evolve constantly rather than being measured in electoral cycles.
The shift, which has seen citizens as creators of content rather than consumers of it, has undermined the centralist view of democracy and created an environment of wiki democracy or crowd sourced democracy. This is at the heart of what is generally known as Web 2.0, and widely considered to be a positive, democratising force. However, we argue, there are worrying elements here too. Government does not always deliver on the promise of the networked society as it involves citizens and others in the process of government. Also a number of key internet companies have emerged as powerful intermediaries harnessing the efforts of the many, and re- using and re-selling the products and data of content providers in the Web 2.0 environment. A discourse about openness and transparency has been offered as a democratising rationale but much of this masks an uneven relationship where the value of online activity flows not to the creators of content but to those who own the channels of communication and the metadata that they produce.
In this context the state is just one stakeholder in the mix of influencers and opinion formers impacting on our behaviours, and indeed our ideas of what is public. The question of what it means to create or own something, and how all these new relationships to be ordered and governed are subject to fundamental change. While government can often appear slow, unwieldy and even irrelevant in much of this context, there remains a need for some sort of political control to deal with the challenges that technology creates but cannot by itself control. In order for the internet to continue to evolve successfully both technically and socially it is critical that the multistakeholder nature of internet governance be understood and acknowledged, and perhaps to an extent, re- balanced. Stakeholders can no longer be classified in the broad headings of government, private sector and civil society, and their roles seen as some sort of benign and open co-production. Each user of the internet has a stake in its efficacy and each by their presence and participation is contributing to the experience, positive or negative of other users as well as to the commercial success or otherwise of various online service providers. However stakeholders have neither an equal role nor an equal share. The unequal relationship between the providers of content and those who simple package up and transmit that content - while harvesting the valuable data thus produced - needs to be addressed. Arguably this suggests a role for government that involves it moving beyond simply celebrating and facilitating the on- going technological revolution. This paper reviews the shifting landscape of stakeholders and their contribution to the efficacy of the internet. It will look to critically evaluate the primacy of the individual as the key stakeholder and their supposed developing empowerment within the ever growing sea of data. It also looks at the role of individuals in wider governance roles. Governments in a number of jurisdictions have sought to engage, consult or empower citizens through technology but in general these attempts have had little appeal. Citizens have been too busy engaging, consulting and empowering each other to pay much attention to what their governments are up to. George Orwell’s view of the future has not come to pass; in fact the internet has insured the opposite scenario has come to pass. There is no big brother but we are all looking over each other’s shoulder all the time, while at the same time a number of big corporations are capturing and selling all this collective endeavour back to us.
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RATIONALE, AIMS AND OBJECTIVES: Health care services offered to the public should be based on the best available evidence. We aimed to explore pharmacy tutors' and trainees' views on the importance of evidence when making decisions about over-the-counter (OTC) medicines and also to investigate whether the tutor influenced the trainee in practice.
METHODS: Following ethical approval and piloting, semi-structured interviews were conducted with pharmacy graduates (trainees) and pharmacist tutors. Transcribed interview data were entered into the NVivo software package (version 10), coded and analysed via thematic analysis.
RESULTS: Twelve trainees (five males, seven females) and 11 tutors (five males, six females) participated. Main themes that emerged were (in)consistency and contradiction, confidence, acculturation, and continuation and perpetuation. Despite having an awareness of the importance and potential benefits, an evidence-based approach did not seem to be routinely or consistently implemented in practice. Confidence in products was largely derived from personal use and patient feedback. A lack of discussion about evidence was justified on the basis of not wanting to lessen patient confidence in requested product(s) or possibly negating the placebo effect. Trainees became acculturated to 'real-life' practice; university teaching and evidence was deemed less relevant than meeting customer expectations. The tutor's actions were mirrored by their trainee resulting in continuation and perpetuation of the same professional attitudes and behaviours.
CONCLUSIONS: Evidence appeared to have limited influence on OTC decision making. The tutor played a key role in the trainee's professional development. More work could be performed to investigate how evidence can be regarded as relevant and something that is consistently implemented in practice.
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RATIONALE: Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors.
OBJECTIVES: To determine whether residential location is associated with risk of first acquisition of P. aeruginosa.
METHODS: We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered.
MEASUREMENTS AND MAIN RESULTS: A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children.
CONCLUSIONS: Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.